CD20+ diffuse large B-cell lymphoma or CD20+ follicular non-Hodgkin’s lymphoma grade 1, 2 or 3a
Conditions
Interventions
Product Name: Mabthera SC
Product Code: RO 45-2294/F04
Pharmaceutical Form: Solution for injection
Sponsors
ROCHE S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for Study entry: 1. Signed, written informed consent form 2. Age = 18 and = 80 years at time of enrolment Rituximab – Roche S.p.A. Protocol ML28881 (MABRELLA) - Version 1, 18 March 2013 45 3. Histologically confirmed, CD20+ DLBCL or CD20+ follicular NHL grade 1, 2 or 3a, according to the WHO classification system 4. Currently being treated with rituximab IV in the Induction or Maintenance setting, having received at least one full dose of rituximab IV, defined as standard full dose of rituximab IV 375 mg/m2 administered without interruption or early discontinuation because of tolerability issues 5. Expectation and current ability for the patient to receive at least four additional cycles of treatment during the Induction phase or six additional cycles of treatment during the Maintenance phase (patients with follicular NHL) 6. Induction only: An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion = 7.5 cm, or Follicular Lymphoma International Prognostic Index (FLIPI) (low, intermediate or high risk) (see Appendix 4) 7. Induction only: At least one bi-dimensionally measurable lesion defined as = 1.5 cm in its largest dimension on computed tomography (CT) scan 8. Eastern Cooperative Oncology Group (ECOG) performance status = 3 (see Appendix 4) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 130 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from Study entry: Cancer-Related Criteria 1. Transformed lymphoma or follicular lymphoma (FL) IIIB 2. Primary central nervous system lymphoma, histologic evidence of transformation to a Burkitt lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, or primary cutaneous DLBCL 3. History of other malignancy that could affect compliance with the protocol or interpretation of results. This includes a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for = 5 years prior to dosing. Note: Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible for the Study. Prior or Concomitant Treatments 4. Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Note: (i) patients receiving corticosteroid treatment with = 30 mg/day of prednisone or equivalent must be on a documented stable dose of at least 4 weeks duration prior to randomization; (ii) a pre-phase of high dose prednisolone (e.g. 100 mg/day for 3 to 5 days) is acceptable for patients with aggressive NHL. Laboratory Assessments at Screening 5. Inadequate renal function, defined as: - Creatinine > 1.5 times the upper limit of normal (ULN) (unless normal creatinine clearance), or calculated creatinine clearance 2.5 x ULN - Total bilirubin = 1.5 x ULN. Note: patients with documented Gilbert disease may be enrolled if total bilirubin is = 3.0 x ULN Other Prior or Current Medical Conditions or Treatments 8. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products 9. For patients with DLBCL - Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone), including prior receipt of anthracyclines 10. Other serious underlying medical conditions, which, in the Investigator‘s judgment, could impair the ability of the patient to participate in the Study (e.g., significant cardiovascular disease, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease) 11. Recent major surgery (within 4 weeks prior to dosing, other than for diagnosis 12. Active and/or severe bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics except if for tumour fever) within 4 weeks prior to dosing 13. Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (must be ruled out during screening): - Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology) Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody [HBcAb] and negative or positive HBsAg with HBV DNA undetectable) may be included. These patients must be followed closely. Patients need to receive antiviral
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective for this Study is as follows: ? To evaluate the incidence of AARs following multiple doses of rituximab SC during Induction and/or Maintenance therapy in patients with CD20+ DLBCL or CD20+ follicular NHL, who have previously received at least one dose of rituximab IV. AARs are defined as all AEs occurring within 24 hours of rituximab SC administration and which are considered related to Study drug. AARs include IIRRs, injection-site reactions, administration site conditions and all symptoms thereof.;Secondary Objective: •To evaluate the safety of rituximab SC •To evaluate the efficacy of rituximab SC •to evaluate the pharmacokinetic of rituximab SC: in FL and DLBCL patients: -population PK parameter, effects of subject characteristics on the rituximab population PK parameters, effects of the covariates related to disease at baseline, interindividual variability,relationship of Ctrough (pre-dose concentration) over time and CR/CRu at 4-8 weeks after the last dose of Induction treatment (concentration defined over time trial), and only for DLBDL patients also rituximab exposures (concentration over time) during the 2 different scheduling of rituximab SC R-CHOP14 or R-CHOP 21 •Patient-reported outcome is measured using Rituximab Administration Satisfaction Questionnaire (RASQ-SC);Primary end point(s): -safety endpoint:AARs, including IIRRs, AEs, AEs of grade = 3, SAEs, routine laboratory parameters, vital signs, concomitant medications, premature withdrawal from the Study and from Study medication due to AEs and ECOG performance status. ;Timepoint(s) of evaluation of this end point: Timepoint of safety endpoints: at every visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Timepoint of efficacy enpoints: at baseline visit, final staging and end of study visit. Timepoint of PK endpoints: DLBCL patients: Induction Collection timelines: 1.Baseline: pre-dose of rituximab SC administration 2.Cycle 7 – Day 1: pre-dose of rituximab SC administration 3.Cycle 7 – Day 7 (± 3 days) 4.Cycle 7 – Day 14 (± 3 days) 4.Cycle 8 – Day 1: pre-dose of rituximab SC administration FL patients: Induction Collection timelines: 1.Baseline: pre-dose of rituximab SC administration 2.Cycle 8 – Day 1: pre-dose of rituximab SC administration Maintenance Collection timelines: 1.Baseline = pre-dose of rituximab SC administration 2.Cycle 12 – Day 1: pre-dose of rituximab SC administration ;Secondary end point(s): -efficay endpoint:the efficacy of rituximab SC will be evaluated during Induction and/or Maintenance in terms of EFS, PFS, CR/Cru, DFS and OS and will be analysed for the FAS and for the Per Protocol populations. -PK endpoint: Descriptive statistics (mean, standard deviation, median and minimum and maximum values), will be computed for all PK parameters: Ctrough, AUC, Cmax, , and CL/F (clearance/fraction of absorbed drug). -patient satisfaction outcome endpoint:Patient-assessed satisfaction will be evaluated using the Rituximab Administration Satisfaction Questionnaire (RASQ-SC). | — |
Countries
Italy
Contacts
Public ContactHEAD OF CLINICAL OPERATIONS
SERGIO SCACCABAROZZI
Outcome results
None listed